The hyperventilation test as a method for developing successful therapy in Prinzmetal's angina.

In 10 cases of Prinzmetal's angina in which episodes of myocardial ischemia were easily and reproducibly induced by hyperventilation, this test was performed 111 times, 41 times under control conditions and 70 times during treatment with one or more of the following drugs: phentolamine, isosorbide dinitrate, propranolol, verapamil, nifedipine and amiodarone. Seventeen of 18 negative tests performed under the influence of a long-acting drug coincided with total remission of the patient's anginal episodes when this drug was administered on a short- or long-term basis. No patient died or sustained infarction during a follow-up period of 10.9 months. A negative test was thus a good indication that the clinical response to the corresponding drug would be favorable. The electrocardiographic changes and chest pain provoked by hyperventilation occurred not when alkalosis was greatest (hydrogen ion [pH] change from 7.42 to 7.58, p less than 0.001), but when pH was approaching normal or control values. The onset of electrocardiographic changes occurred an average of 175 seconds after the end of hyperventilation and, in two cases, the time lag was as much as 480 and 705 seconds, respectively. This raises several questions regarding the true mechanism triggering coronary spasm under such conditions. The hyperventilation test appears to be a useful and safe procedure for selecting the best possible drug for long-term treatment of Prinzmetal's angina as well as for comparing the relative efficacy of different drugs.

Long-term management of sustained, recurrent, symptomatic ventricular tachycardia with amiodarone.

Twenty-three patients with sustained, recurrent, symptomatic ventricular tachycardia were treated with oral amiodarone. Initial doses were 600-2000 mg/day and maintenance doses were 200-1200 mg/day. Amiodarone was highly effective in 20 patients (87%), seven of whom had a follow-up of 30 months or longer, including two who were followed for 5 years. Three patients died within the first 45 days, three died suddenly after a follow-up of 33.5 months, and four had a nonarrhythmic death after a follow-up of 25 months. Fifteen patients (65%) had no recurrence during a follow-up of 21.5 months, while five (22%) had isolated recurrences during a follow-up of 32.2 months. The average maintenance dose was 713 mg/day in the 15 patients who did not have recurrences and 375 mg/day in the five patients who had recurrences (p less than 0.001). Both short- and long-term tolerance were excellent and there was not a single case in which treatment had to be discontinued. The main disadvantage of amiodarone was that it took an average of 9.5 days to reach anti-arrhythmic efficacy. The main advantages were prolonged duration of action (recurrences occurred only 15-60 days after the drug was discontinued or the dose lowered, virtual absence of contraindications, doses as high as 2000 mg/day were safe and patient compliance was excellent.

Abnormal Q waves in right sided chest leads provoked by onset of right bundle-branch block in patients with anteroseptal infarction.

In five cases of anteroseptal myocardial infarction complicated by intermittent right bundle-branch block, the onset of right bundle-branch block provoked the appearance of abnormal Q waves in leads V1 and V2, whereas a small initial R wave was present in the same leads during normal conduction. The intermittency of the conduction disturbance indicated that the Q waves were "right bundle-branch block dependent". It was also apparent that right bundle-branch block shifted the electrical location of the infarct towards the right, and made it look much larger. Right bundle-branch block dependent Q waves may arise during the acute stage of an anterior infarct suggesting, fallaciously, that an acute extension has occurred, or during the chronic stage, leading to the erroneous supposition that a new infarct had developed. The abnormal Q waves anteroseptal infarction complicated by fixed right bundle-branch block, though obviously related to the infarct, may be dependent on the right bundle-branch block.

Low urinary 6-sulphatoxymelatonin levels in patients with coronary artery disease.

A decrease in nocturnal serum melatonin levels was reported in patients with clinically uncharacterized coronary artery disease. To assess whether there was a correlation between melatonin production and disease stage, we measured the nocturnal urinary excretion of 6-sulphatoxymelatonin (an index of blood melatonin concentration) in patients with chronic stable or unstable coronary disease and in a group of age-matched controls. Three groups of individuals were studied: a) 24 healthy subjects (mean age: 63 +/- 13 yr); b) 32 patients with chronic, stable, coronary disease (62 +/- 11 yr); and c) 27 patients with unstable angina (62 +/- 12 yr). For 6-sulphatoxymelatonin measurement, urine was collected from 18:00 to 06:00 hr, within 48 hr of hospitalization in the case of unstable angina. 6-Sulphatoxymelatonin was measured by a specific radioimmunoassay. Urinary 6-sulphatoxymelatonin excretion was significantly lower in unstable angina patients than in healthy subjects or in patients with stable angina. 6-Sulphatoxymelatonin correlated negatively with age in healthy subjects, but not in coronary patients. 6-Sulphatoxymelatonin excretion in patients treated with beta-adrenoceptor blockers did not differ significantly from coronary patients not receiving beta-blockers. The results indicate that patients with coronary disease have a low melatonin production rate, with greater decreases in those with higher risk of cardiac infarction and/or death.

Efficacy of amiodarone during long-term treatment of potentially dangerous ventricular arrhythmias in patients with chronic stable ischemic heart disease.

Amiodarone was administered orally to 30 patients with chronic stable coronary artery disease and severe ventricular arrhythmias. Control studies revealed frequent (more than 30/hr) ventricular premature beats (VPBs) (27 patients), bigeminy (21 patients), couples (29 patients), R-on-T phenomenon (14 patients), ventricular tachycardia (16 patients), and ventricular fibrillation (1 patient). Two 24-hour Holter recordings and stress tests were performed before treatment, and an average of 3.6 per patient were done during treatment. Amiodarone caused suppression of all ventricular arrhythmias in 13 (43%) of the 30 patients and suppression of all complex forms and greater than 90% reduction of VPB number in 14 patients (47%) during a follow-up of 12.4 months. The mean dose was 590 mg/day in the 27 responders and 300 mg/day in the three nonresponders. A similar antiarrhythmic response was observed during stress testing. One of the 30 patients died due to massive pulmonary embolism and no arrhythmias were detected. In addition, amiodarone suppressed the occurrence of anginal pain and effort-induced ST changes in 9 of 10 patients and in 11 of 13 patients, respectively. The rate-pressure product and peak heart rate were significantly reduced in all patients. Our results suggest that amiodarone may be ideally suited for treatment of ventricular arrhythmias and for possible prevention of sudden death in patients with ischemic heart disease.

Morbidity and mortality following early administration of amiodarone in acute myocardial infarction. GEMICA study investigators, GEMA Group, Buenos Aires, Argentina. Grupo de Estudios Multicéntricos en Argentina.

AIMS: The objective of this study was to ascertain the effect of intravenous and oral amiodarone on morbidity and mortality in patients during the first hours after the onset of an acute myocardial infarction. METHODS AND RESULTS: A cohort of 1073 patients admitted to the CCU within 24 h of the onset of symptoms of an acute myocardial infarction and heart failure (Killip and Kimball A-B) were randomized to receive amiodarone (n=542) or placebo (n=531) for 6 months. Because of the higher mortality, on an interim analysis, from a 'high dose' of amiodarone or placebo (516 patients) the protocol was changed to a 'low dose' or placebo (557 patients). Mortality with high doses of amiodarone was 16.30% vs 10.16% in the placebo group (P=0.04), whereas mortality with low doses was 6.61% vs 9.47% in the control group (P=0.20). Several non-fatal adverse effects were observed in 108 and 73 patients treated with amiodarone and placebo, respectively. CONCLUSION: This study demonstrated that early administration of amiodarone in low doses to patients with an acute myocardial infarction may be used only if life-threatening arrhythmia justify its prescription. Conversely, when given in high doses, it might increase mortality.